Modified .beta..sub.2 m-microglobulin (m.beta..sub.2 m) is a variant of .beta..sub.2 -microglobulin (.beta..sub.2 m), which variant has been detected in connection with a variety of types of cancer and disorders of the immune system.
Its precursor .beta..sub.2 m is a serum protein with a molecular mass of 11800 Daltons consisting of a single chain polypeptide consisting of 99 amino acid residues with a disulfide bridge between cysteine residues in positions 25 and 80, and with a known amino acid sequence (1). Structurally .beta..sub.2 m shows a marked homology to the constant domain in IgG, especially the C.sub.H 3 domain and the .alpha..sub.3 domain of the heavy chain HLA-B7. .beta..sub.2 m is part of the major histocompatibility complex on cell membranes and is present in free form in body fluids such as serum, spinal fluid, saliva, semen, and colostrum (2,3). In healthy individuals the serum concentration of .beta..sub.2 m is 50-200 nmol/1 (4).
The serum concentration of .beta..sub.2 m is elevated in a variety of diseases e.g. rheumatoid arthritis (RA), systemic lupus erythomatosus (SLE), malignant lymphoma (ML), and certain types of lung cancer such as small cell lung cancer (SLC) (5-7). High levels of serum .beta..sub.2 m in ML decrease during response to chemotherapy, while relapse is generally not accompanied by rising serum .beta..sub.2 m.
Small cell lung cancer (SLC) is nearly always disseminated at the time of diagnosis and therefore the main treatment is combination chemotherapy. With chemotherapy it is possible to induce remission in more than 80% of all patients, but in most of the cases the tumor will later escape control. The earliest possible diagnosis, preferably at a stage where the disease is still localized, may consequently be crucial for improving the rate of survival of patients suffering from SLC.
Acquired immunodeficiency syndrome (AIDS) is the final culmination of a disease that apparently exists in other forms such as AIDS-related complex or lymphadenopathy syndrome, and in less-manifested states, including the carrier state. Blood-donor screening by use of an antibody to the presumed causative virus (HTLV-III/LAV) has begun. Such testing for the virus only detects exposure to it, not the presence of or the prognosis for development of disease. Also, the antibody test for HTLV-III sometimes fails to detect the presence of the virus (1). Thus, another test is needed that will allow a more quantitative assessment of the response of the immune system to HTLV-III exposure.
.beta..sub.2 m has received much attention as a possible marker that could be used for diagnosis and monitoring of diseases such as those mentioned above.
It has thus been reported that most AIDS patients tested have .beta..sub.2 m levels above normal. It has further been reported that increased .beta..sub.2 m levels have been found in a number of cases even two years before clinical diagnosis of AIDS.
Incubation in vitro of serum from patients with RA, SLE, germ cell tumors and ML have been shown to result in the appearance in crossed radioimmunoelectrophoresis (CRIE) of a .beta..sub.2 m fraction with ".alpha.-electrophoretic mobility" (5,8,9). In patients with ML an inverse correlation between the amount of this .alpha.-fraction and response to chemotherapy has been found.
Ravi B. Bhalla et al.: Clinical Chemistry 31 (1985) p. 1411, have reported that they found the .alpha.-electrophoretic form of .beta..sub.2 m or modified .beta..sub.2 m to be present in all their AIDS patients including those with normal .beta..sub.2 m levels, and beside that also in a patient who was HTLV-III-negative.
The .alpha.-electrophoretic form or modified .beta..sub.2 m (m.beta..sub.2 m) therefore seems very attractive as a marker for a variety of immunological disorders. M.beta..sub.2 m is obviously not specific for any of the diseases mentioned above, but measurement thereof will nevertheless be a valuable tool for screening of a large number of samples, or for monitoring of the development of those diseases.